Anaplastic myeloma presenting as mandibular swelling: Diagnosis by cytology.

Multiple myeloma is a disease resulting from clonal proliferation of plasma cells. A disease of the elderly, jaw lesions are seen in 14% of patients affected with myeloma. Rarely the oral and maxillofacial lesions can be the first manifestation of the disease. We report the case of a 75-year-old man who presented with mandibular swelling. Fine-needle aspiration cytology was done from the swelling and smears were suggestive of anaplastic myeloma, which is a rare and aggressive variant of myeloma. The diagnosis of a plasmacytoma was confirmed by biopsy. Further workup of the patient revealed osteolytic lesions in skull, M band in electrophoresis and evidence of renal failure. Peripheral smear and bone marrow findings were also consistent with myeloma.

Introduction

Plasma cell neoplasms result from expansion of a single clone of immunoglobulin secreting plasma cells. Plasma cell myeloma is characterized by presence of a monoclonal protein in the serum or urine or both, with anemia, osteolytic lesions, bone pain, hypercalcemia, and renal failure. Myeloma is a disease predominantly of the elderly.

Osteolytic lesions in the jaw are seen in more than 30% of patients with multiple myeloma.[1] The oral manifestations of multiple myeloma can be the first sign of the disease in 14% of the patients. We present the case of a 75-year-old man diagnosed with anaplastic myeloma whose initial presentation was a mandible swelling.

Case Report

The present case is about a 75-year-old male patient who presented with a firm swelling on the left side of the cheek measuring 10 cm × 8 cm × 5 cm since 1 month with a gradual increase in size and associated with pain. A destructive lesion in the left side of mandible was seen in the orthopantomogram. Computed tomography scan displayed a soft tissue mass involving the ramus of mandible destroying the bone. After obtaining informed consent fine-needle aspiration was done from the swelling and slides were stained with May-Grünwald-Giemsa. Smears showed plasma cells arranged in diffuse sheets and singly scattered [Figure 1]. Many cells were highly pleomorphic and showed nuclear and cytoplasmic budding [Figure 1-inset]. Few binucleate and multinucleate forms were also seen. Some cells had high nucleocytoplasmic ratio with prominent nucleoli suggesting a plasmablastic nature. With this picture a possibility of an anaplastic/plasmablastic myeloma was suggested. Biopsy was done and the histopathology sections confirmed a diagnosis of plasmacytoma. Anaplastic areas were noted in some areas. A further workup of the patient was done for multiple myeloma. Radiograph of the skull registered multiple osteolytic lesions. Serum protein electrophoresis revealed a high β globulin fraction.

Figure 1

Aspirate smears showing plasma cells (MGG, ×1000). Inset — plasma cells with anaplastic morphology (MGG, ×1000)

Investigations showed a raised erythrocyte sedimentation rate (65 mm/1st hr) and evidence of renal failure. Urine examination demonstrated hematuria and proteinuria.

Peripheral smear examination showed rouleaux formation with pancytopenia. Bone marrow aspirate evinced 75% plasmacytosis with sheets of plasma cells and some cells showing dysplastic features and plasmablastic nature similar to that seen in the cytology smears. The patient was subjected to multiple cycles of dialysis because of the impending renal failure. Chemotherapy could not be started and the patient died 2 months after diagnosis of myeloma.

Discussion

B-cell lymphoid tissue neoplasms with plasma cell differentiation can broadly be classified into three types-multiple myeloma, solitary plasmacytoma and extramedullary plasmacytoma. Multiple myeloma presents in the disseminated form, affecting several bones.[2] Solitary plasmacytoma differs from multiple myeloma by being a solitary soft tissue or bone lesion with no systemic symptoms of multiple myeloma and less than 10% plasma cells in the bone marrow.[1] Extramedullary plasmacytomas arise in tissues other than bone. The most common bones affected by multiple myeloma are the vertebrae, ribs, skull, mandible, clavicles, scapula and the pelvis. The involvement of mandible is infrequent but is even rarer to be involved as the first bone affected. Plasmacytomas of bone constitute 5% of plasma cell neoplasms. Incidental discovery of lesions in the jaw may be the first evidence of this disease.

Aspirate smears of plasmacytoma show sheets of plasma cells which have a morphologic spectrum ranging from well-differentiated to anaplastic or blastic.[3] The well-differentiated plasma cells resemble normal plasma cells and have round to oval eccentric nuclei with a cartwheel chromatin, dense basophilic cytoplasm and perinuclear clear zone in Giemsa slides. Plasmablastic morphology is characterized by a high nucleocytoplasmic ratio, round nuclei, fine chromatin, and prominent nucleoli. The neoplastic plasma cells assuming the form of anaplastic large cells or signet ring cells can mimic metastatic carcinoma. However, the presence of a cogwheel chromatin and prominent Golgi zone in at least some of the tumor cells will help in the cytological diagnosis.[4] Anaplastic myeloma is characterized by the presence of pleomorphic and multinucleate plasma cells with brisk mitotic activity and atypical mitotic figures.[3] When there is diagnostic difficulty a careful search will usually show that even in anaplastic myeloma some cells show clear signs of plasmacytic differentiation.

Anaplastic pleomorphic plasma cells are likely to cause confusion when a primary bone origin is unsuspected. Plasmacytomas with anaplastic morphology has to be differentiated from poorly differentiated neoplasms arising from any cell lineage and melanoma.[5] Immunostains for S100, Melan A or HMB 45 will help in diagnosis of melanoma. A pan-cytokeratin like AE1/AE3 will distinguish anaplastic myeloma from undifferentiated carcinoma.[5]

Literature review has shown that anaplastic plasmacytomas can develop in immunosuppression and Epstein-Barr virus infection.[67] Reactive plasmacytosis in bone marrow is a common finding in HIV infection, but highly aggressive myeloma can occur rarely in HIV patients.[6] In a study by Bangerter et al.,[8] it was seen that majority of extramedullary plasmacytomas showed an anaplastic morphology. Anaplastic plasmacytoma occurring in extramedullary sites pose a diagnostic difficulty. A thorough evaluation of the cytologic smears will help in reaching at a correct diagnosis.

Conclusion

Plasmacytoma of the mandible can occur as first evidence of multiple myeloma. Anaplastic myeloma which is a rare and aggressive variant of myeloma mimic poorly differentiated carcinoma. An extensive search for cells with plasmacytic differentiation with recognition of diagnostic features of anaplastic myeloma is important so as not to miss the diagnosis. This is more important when plasmacytomas occur in rare sites like mandible without a previous history of myelomatosis. Fine-needle aspiration cytology which is minimally invasive and inexpensive can be used as a front line investigative method in diagnosis of plasmacytoma.